We propose to continue the National Center for Biomedical Ontology (NCBO), which develops tools and methods for assimilating, archiving, accessing, and applying machine-processable representations of biomedical domain objects, processes, and relations to assist in the management, integration, visualization, analysis, and interpretation of the huge, distributed data sets that are now the hallmark of biomedical research and clinical care. Our center is truly national in scope, with participation of leading scientific groups at Stanford, Mayo Clinic, University at Buffalo, and the University of Victoria. Our objectives are defined by the following six Cores: (1) the development of enhanced computational methods for management of ontologies and controlled terminologies using current Web standards; integration of ontology authoring, publishing, and peer review; creation of a comprehensive ontology-based index of publicly available data resources; development of new analytic methods to summarize and profile biomedical data; (2) the promotion of Driving Biological Projects that can stimulate our research by suggesting new requirements and offering new test beds for deployment-initially involving the Cardiovascular Research Grid, the Rat Genome Database, the caNanoLab nanoparticle database, and the i2b2 National Center for Biomedical Computing, and later engaging the WHO's development of lCD-11, studies performed by ArrayExpress, and projects that will be selected via open requests for applications; (3) the maintenance of a computational infrastructure to support our research, development, and dissemination activities; provision of user support to the growing number of researchers and clinicians who use our technologies; (4) the training of the next generation of scientists in biomedical ontology; (5) a comprehensive set of dissemination activities, that include workshops, tutorials. Web-based seminars, and a major international conference; and (6) outstanding project administration conducted by a dedicated and talented management team. The NCBO will accelerate the transition of biomedicine into the world of e-science, facilitate the creation of a National Health Information Infrastructure, and extend a network of collaboration through its interactions with other NCBCs, with other research consortia, and with the biomedical community at large.